Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death

Abstract Proximal tubular cells (PTC) are particularly vulnerable to hypoxia-induced apoptosis, a relevant factor for kidney disease. We hypothesized here that PTC death under hypoxia is mediated by cyclo-oxygenase (COX-2)-dependent production of prostaglandin E2 (PGE2), which was confirmed in human...

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Main Authors:	Coral García-Pastor, Selma Benito-Martínez, Ricardo J. Bosch, Ana B. Fernández-Martínez, Francisco J. Lucio-Cazaña
Format:	article
Language:	EN
Published:	Nature Portfolio 2021
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/f711417c43074f3f8a7eb7b6f2956e11
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spelling	oai:doaj.org-article:f711417c43074f3f8a7eb7b6f2956e112021-12-02T13:26:58ZIntracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death10.1038/s41598-021-86219-w2045-2322https://doaj.org/article/f711417c43074f3f8a7eb7b6f2956e112021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86219-whttps://doaj.org/toc/2045-2322Abstract Proximal tubular cells (PTC) are particularly vulnerable to hypoxia-induced apoptosis, a relevant factor for kidney disease. We hypothesized here that PTC death under hypoxia is mediated by cyclo-oxygenase (COX-2)-dependent production of prostaglandin E2 (PGE2), which was confirmed in human proximal tubular HK-2 cells because hypoxia (1% O2)-induced apoptosis (i) was prevented by a COX-2 inhibitor and by antagonists of prostaglandin (EP) receptors and (ii) was associated to an increase in intracellular PGE2 (iPGE2) due to hypoxia-inducible factor-1α-dependent transcriptional up-regulation of COX-2. Apoptosis was also prevented by inhibitors of the prostaglandin uptake transporter PGT, which indicated that iPGE2 contributes to hypoxia-induced apoptosis (on the contrary, hypoxia/reoxygenation-induced PTC death was exclusively due to extracellular PGE2). Thus, iPGE2 is a new actor in the pathogenesis of hypoxia-induced tubular injury and PGT might be a new therapeutic target for the prevention of hypoxia-dependent lesions in renal diseases.Coral García-PastorSelma Benito-MartínezRicardo J. BoschAna B. Fernández-MartínezFrancisco J. Lucio-CazañaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Coral García-Pastor Selma Benito-Martínez Ricardo J. Bosch Ana B. Fernández-Martínez Francisco J. Lucio-Cazaña Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
description	Abstract Proximal tubular cells (PTC) are particularly vulnerable to hypoxia-induced apoptosis, a relevant factor for kidney disease. We hypothesized here that PTC death under hypoxia is mediated by cyclo-oxygenase (COX-2)-dependent production of prostaglandin E2 (PGE2), which was confirmed in human proximal tubular HK-2 cells because hypoxia (1% O2)-induced apoptosis (i) was prevented by a COX-2 inhibitor and by antagonists of prostaglandin (EP) receptors and (ii) was associated to an increase in intracellular PGE2 (iPGE2) due to hypoxia-inducible factor-1α-dependent transcriptional up-regulation of COX-2. Apoptosis was also prevented by inhibitors of the prostaglandin uptake transporter PGT, which indicated that iPGE2 contributes to hypoxia-induced apoptosis (on the contrary, hypoxia/reoxygenation-induced PTC death was exclusively due to extracellular PGE2). Thus, iPGE2 is a new actor in the pathogenesis of hypoxia-induced tubular injury and PGT might be a new therapeutic target for the prevention of hypoxia-dependent lesions in renal diseases.
format	article
author	Coral García-Pastor Selma Benito-Martínez Ricardo J. Bosch Ana B. Fernández-Martínez Francisco J. Lucio-Cazaña
author_facet	Coral García-Pastor Selma Benito-Martínez Ricardo J. Bosch Ana B. Fernández-Martínez Francisco J. Lucio-Cazaña
author_sort	Coral García-Pastor
title	Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
title_short	Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
title_full	Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
title_fullStr	Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
title_full_unstemmed	Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
title_sort	intracellular prostaglandin e2 contributes to hypoxia-induced proximal tubular cell death
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f711417c43074f3f8a7eb7b6f2956e11
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Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death

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